Neurotoxic side effects in children with refractory or relapsed T-cell malignancies treated with nelarabine based therapy
The prognosis in children with refractory or relapsed (r/r) T-cell acute lymphoblastic leukaemia (T-ALL) or lymphoblastic lymphoma (T-LBL) is poor. Nelarabine (Ara-G) has successfully been used as salvage therapy in these children, but has been associated with significant, even fatal, neurotoxicities. We retrospectively analysed 52 patients with r/r T-ALL/T-LBL aged ≤19 years who were treated with Ara-G alone (n = 25) or in combination with cyclophosphamide and etoposide (n = 27). The majority of patients (45/52) received 1–2 cycles of Ara-G. Seventeen patients (32·7%) had refractory disease, 28 (53·8%) were in first relapse and 7 (13·5%) were in second relapse. A response to Ara-G was achieved in 20 patients and 15 (28·8%) were in remission at last follow-up. Twelve patients (23·1%) had neurotoxic adverse effects (neuro-AE) of any grade, of whom 7 (13·5%) developed neurotoxicity ≥ grade III. The most frequent neuro-AEs were peripheral motor neuropathy (19·2%), peripheral sensory neuropathy (11·5%) and seizures (9·6%). Three patients died of central neuro-AE after 1–2 cycles of combination therapy. Patients with neurotoxicity were significantly older (median 15·17 years) than those without (10·34 years, P = 0·017). No differences were observed between mono- and combination therapy concerning outcome and neuro-AE. The incidence of neuro-AE was not associated with concurrent intrathecal therapy or prior central nervous system irradiation.
|Keywords||Ara-G, nelarabine, neurotoxicity, T-ALL, T-LBL|
|Persistent URL||dx.doi.org/10.1111/bjh.14877, hdl.handle.net/1765/107985|
|Journal||British Journal of Haematology|
Kuhlen, M. (Michaela), Bleckmann, K. (Kirsten), Möricke, A, Schrappe, M. (Martin), Vieth, S. (Simon), Escherich, G, … Chen-Santel, C. (Christiane). (2017). Neurotoxic side effects in children with refractory or relapsed T-cell malignancies treated with nelarabine based therapy. British Journal of Haematology, 179(2), 272–283. doi:10.1111/bjh.14877